The purpose of the research program is to optimize the treatment of human cancer with combination chemotherapy by analyzing interactions of two or more drugs given in different regimens in treatment of one or more animal tumor systems. Manipulation of the drug regimens will involve both variations in dose and time sequence of administration of the drugs. Analysis by adaptation of currently available response surface methodology will provide information that will enable extrapolation of in vitro and in vivo data currently obtainable for single drugs and for some drug combinations for use in rational modifications of existing clinical protocols and for suggesting new combinations of drugs for clinical use. We propose to study combinations of drugs that are being used clinically and other combinations showing strong interactions in screening systems. Tumor systems to be primarily employed will be L1210 leukemia and P388 leukemia. The methods developed for analysis of actions and interactions of combinations of drugs may serve as a model that can be adapted to analysis of clinical studies of similar design.